The study of the prevention of pregnancy in human females has led to the evolution of many hormone-based compositions. Some compositions contain both estrogenic and progestogenic compounds. Such compositions, referred to herein as "estrogen/progestogen combinations", are highly effective in controlling ovulation and conception.
It has long been recognized that the progestin component is primarily responsible for the efficacy of the combination oral contraceptive. When original researchers attempted to synthesize pure progesterone, estrogen was a common contaminant. It was at this point that researchers realized that small quantities of estrogen could significantly minimize the major unwanted side effect, breakthrough bleeding or spotting. Small amounts of estrogen helped stabilize the endometrium and allowed cyclic withdrawal bleeding, similar to the natural menstrual cycle. Initially, the doses of estrogen in combination oral contraceptives were quite high (150 mcg). To minimize estrogen's major negative side effect on blood clotting factors, the dose of estrogen was reduced over time (30-35 mcg). However, as estrogen doses decreased, the incidences of unwanted breakthrough bleeding or spotting have generally increased. Most recently a new family of oral contraceptives (multiphasics) have been introduced that mimic the natural rise of progesterone over the cycle in an attempt to solve this problem. The present invention relates to the discovery that the side effects of breakthrough bleeding or spotting can be minimized by (1) a gradual increase of the estrogenic component throughout the cycle, (2) an increase of the ratio of estrogen/progestin throughout the cycle, (3) administration of those combinations at appropriately-timed intervals.